The therapeutic value of L-dopa in the treatment of Parkinsonism is now well established. Orally administered L-dopa is absorbed by the intestine, but significant amounts of the drug are metabolized by the gastric mucosa, never reaching the blood as the beneficial form, capable of traversing the blood-brain barrier (Rivera-Calimlim et al., 1971; Bainchine et al., 1971). The central thrust of this research proposal concerns the morphological (gross, histological and fine structural), histochemical (intracellular lipid) and cytochemical fine structural localization of phosphatases) alterations of the adrenal glands, both cortex and medulla, and gastrointestinad tract, both stomach and intestine, induced by chronic L-dopa therapy in the rat. The physiological and biochemical counterparts to this multifaceted approach will be contributed by the co-investigators. To differentiate those alterations specific to L-dopa, other drugs (e.g. phenobarbital) will be substituted for L-dopa in the experimental regimen. To ascertain whether or not the L-dopa-induced variations in the rat gastric mucosa are similar to those which occur in humans on long-terms L-dopa therapy, biopsies of gastric mucosae of Parkinsonians will be prepared for analysis with the electron microscope. Considerable clinical data exist for which the proposed morphological and cytochemical study may provide structural-functional insight at the cellular level.